A compartmental pharmacokinetic evaluation of long-acting rilpivirine in HIV-negative volunteers for pre-exposure prophylaxis

A. G A Jackson, L. J. Else, P. M M Mesquita, D. Egan, D. J. Back, Z. Karolia, L. Ringner-Nackter, C. J. Higgs, Betsy Herold, B. G. Gazzard, M. Boffito

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Abstract

Rilpivirine long-acting (RPV-LA) is a parenteral formulation enabling prolonged plasma exposure. We explored its multiple-compartment pharmacokinetics (PK) after a single dose, for pre-exposure prophylaxis. Sixty-six HIV-negative volunteers were enrolled: women received an intramuscular dose of 300, 600, or 1,200 mg, with plasma and genital levels measured to 84 days postdose; men receiving 600 mg had similar PK determined in plasma and rectum. Ex vivo antiviral activity of cervicovaginal lavage (CVL) was also assessed. After a single dose, RPV concentrations peaked at days 6-8 and were present in plasma and genital-tract fluid to day 84. Vaginal and male rectal tissue levels matched those in plasma. At the 1,200 mg dose, CVL showed greater antiviral activity, above baseline, at days 28 and 56. All doses were well tolerated. All doses gave prolonged plasma and genital-tract rilpivirine exposure. PK and viral inhibition of repeated doses will be important in further dose selection.

Original languageEnglish (US)
Pages (from-to)314-323
Number of pages10
JournalClinical Pharmacology and Therapeutics
Volume96
Issue number3
DOIs
StatePublished - 2014

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Rilpivirine
Volunteers
Pharmacokinetics
HIV
Therapeutic Irrigation
Antiviral Agents
Rectum
Pre-Exposure Prophylaxis

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

A compartmental pharmacokinetic evaluation of long-acting rilpivirine in HIV-negative volunteers for pre-exposure prophylaxis. / Jackson, A. G A; Else, L. J.; Mesquita, P. M M; Egan, D.; Back, D. J.; Karolia, Z.; Ringner-Nackter, L.; Higgs, C. J.; Herold, Betsy; Gazzard, B. G.; Boffito, M.

In: Clinical Pharmacology and Therapeutics, Vol. 96, No. 3, 2014, p. 314-323.

Research output: Contribution to journalArticle

Jackson, AGA, Else, LJ, Mesquita, PMM, Egan, D, Back, DJ, Karolia, Z, Ringner-Nackter, L, Higgs, CJ, Herold, B, Gazzard, BG & Boffito, M 2014, 'A compartmental pharmacokinetic evaluation of long-acting rilpivirine in HIV-negative volunteers for pre-exposure prophylaxis', Clinical Pharmacology and Therapeutics, vol. 96, no. 3, pp. 314-323. https://doi.org/10.1038/clpt.2014.118
Jackson, A. G A ; Else, L. J. ; Mesquita, P. M M ; Egan, D. ; Back, D. J. ; Karolia, Z. ; Ringner-Nackter, L. ; Higgs, C. J. ; Herold, Betsy ; Gazzard, B. G. ; Boffito, M. / A compartmental pharmacokinetic evaluation of long-acting rilpivirine in HIV-negative volunteers for pre-exposure prophylaxis. In: Clinical Pharmacology and Therapeutics. 2014 ; Vol. 96, No. 3. pp. 314-323.
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